Capillary malformation-arteriovenous malformation syndrome Q85.8

Capillary malformation-arteriovenous malformation syndrome(CM-AVM) is a complex disorder of the vascular system of the body. The syndrome is characterized by capillary malformations (CMs) of the skin(nevus flammeus/port wine stain). These patches are usually visible at birth, become more severe during childhood, but do not usually cause health problems.

In some people with CM-AVM, the cutaneous capillary malformations are the only sign of the disease. Others have associated arteriovenous malformations (AVMs) and/or arteriovenous fistulas (AFVs), fast-flowing vascular abnormalities that typically occur in the skin, muscle, bone, spine, and brain; life-threatening complications of these lesions may include bleeding, congestive heart failure, and/or neurologic sequelae.

CM-AVM is thought to occur in at least 1 in 100,000 people of Northern European origin. The prevalence of the disease in other populations is unknown.

CM-AVM is caused by mutations in the RASA1 gene . This gene provides instructions for the production of a protein known as p120-RasGAP, which is involved in the transmission of chemical signals from outside the cell to the nucleus. These signals help control several important cellular functions, including cell growth and division (proliferation), the process by which cells mature to perform specific functions (differentiation), and cell movement. The role of the p120 RasGAP protein is not fully understood, although it appears to be essential for normal vascular development.

Mutations in the RASA1 gene result in the production of a nonfunctional version of the p120-RasGAP protein. Loss of activity of this protein disrupts tightly regulated chemical signaling during development. However, it is unclear how these changes lead to the specific vascular abnormalities seen in people with CM-AVM.

The disease is inherited in an autosomal dominant manner. This means that one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from an affected parent. Other cases arise from new mutations in the gene and occur in people who do not have the disorder in their family.

Arteriovenous malformations (AVMs) and arteriovenous fistulas (AVFs) are abnormal connections between arteries, veins, and capillaries that affect blood circulation. Depending on where they occur in the body, these abnormalities can be associated with complications such as sudden abnormal bleeding, migraine headaches, seizures, and cardiovascular complications including heart failure.

In people with CM-AVM, the complications of AVMs and AVFs occur in infancy or early childhood; however, some of these vascular abnormalities never cause any symptoms.

Phenotypically, CM-AVM syndrome resembles Parkes-Weber syndrome or Klippel-Trénaunay syndrome. However, both vascular malformation syndromes usually find "overgrowth" of limbs.

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